01502-A: Myxoma virus oncolytic therapy in mouse models of canine cancer
Grant Status: Closed
Project SummaryNovel cancer treatments are needed to minimize patient discomfort caused by cancer therapy and eliminate failure of current treatment modalities. The use of oncolytic viral vectors is an exciting therapeutic option that deserves further study. This project was designed to determine if the poxvirus, myxoma virus (MYXV), can be used to eliminate cancer cells and prevent the spread of tumors throughout the body. Poxviruses have several characteristics that make them ideal cancer therapeutics: 1) they target neoplastic lesions where leaky vessels are formed; 2) they are easily engineered to express antitumor agents; 3) they elicit a strong immune response which can be used to target abnormal cells; and 4) they are effectively cleared from the body by antibodies, preventing latent or recurrent infection. MYXV is a poxvirus that does not cause disease in any animal except the rabbit. However, MYXV does grow in some cancer cells. Since MYXV only grows in abnormal cells, virus replication in healthy tissue should not occur. This project aimed to evaluate the anticancer effects of MYXV in mouse models of canine cancer. If the tumors can be reduced in size or eliminated, these studies may lead to the use of genetically modified poxviruses as cancer treatments in companion animals. This grant provided key preliminary data which made further analysis of vaccinia virus therapy in a xenograft model of canine soft tissue sarcoma possible. Histopathological results indicated that all of the masses that developed after subcutaneous tumor cell inoculation in B6.Cg-Foxn1nu /J mice were comprised of lymphoid tissue with no tumor cells present in the lymphoid tissue or any other tissue. A possible, explanation for lack of tumor development may be the innate immune response consisting of circulating natural killer cells, dendritic cells, and/or macrophages present in this mouse strain. Importantly, STSA-l cells were tumorigenic in NCI/Hsd/Athymic Nude - Foxn1nu mice indicating that STSA-l cells isolated from a canine soft tissue sarcoma are indeed cancerous cells. Ongoing genetic experiments to collaborate this statement are currently being performed with the help of Dr. Thamm (Colorado State University). Significant tumor reduction was achieved with one intravenous dose of a recombinant vaccinia virus in the STSA-1 NCI/Hsd/Athymic Nude - Foxn1nu mouse model of canine soft tissue sarcoma. No side effects were observed with this treatment. The success using a recombinant vaccinia virus to treat mice harboring canine soft tissue sarcomas provides the groundwork for clinical trials in dogs with this type of invasive cancer. It is likely that the other primary canine cancer cells used in this project are tumorigenic in different nude mouse strains. It is important to continue investigating these canine cancer cells in murine models for the purpose of evaluating the oncolytic potential of oncolytic virus treatment in canine cancer patients that are refractory to more traditional cancer therapeutics.
Publication(s)- Gentschev I, Adelfinger M, Josupeit R, Rudolph S, Ehrig K, Weibel S, Chen N, Yu VA, Zhang Q, MacNeill AL, Stritzker J, Szalay AA. Preclinical evaluation of oncolytic vaccinia virus for therapy of canine soft tissue sarcoma. In preparation.
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